Triethylamine → HCID 18396233, compound

HRID 611589Notes

Reaction equation

HRID 611589 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4](I)[C:3]=1[OH:9].CCN(CC)CC.[C:17]([N:24]1[CH2:28][CH2:27][CH2:26][C@H:25]1[C:29]#[CH:30])([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].C([O-])(O)=O.[Na+]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[C:17]([N:24]1[CH2:28][CH2:27][CH2:26][C@H:25]1[C:29]1[O:9][C:3]2[C:4](=[N:5][CH:6]=[CH:7][C:2]=2[Cl:1])[CH:30]=1)([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 11030701(S)-N-Boc-2-ethynylpyrrolidineHCID 195976654-Chloro-2-iodopyridin-3-ol

Product 1

HCID 18396233HCID 18396233, compoundYield 14%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 4-chloro-3-hydroxy-2-iodopyridine (1.04 g, 4.10 mmol) in DMF (10 mL) was added (Ph3P)2PdCl2 (0.140 g, 0.20 mmol), CuI (0.152 g, 0.80 mmol) and Et3N (0.496 g, 4.90 mmol). The mixture was stirred at room temperature for one hour. A solution of 1-Boc-2-(S)-ethynylpyrrolidine (0.80 g, 4.10 mmol), from step 1c above, in DMF (10 mL) was added and the mixture was heated at 60° C. for 16 hours. The reaction mixture was cooled to room temperature and poured into saturated NaHCO3 and washed with Et2O (4×100 mL). The combined organic extracts were washed with brine/H2O (1/1 400 mL), dried (MgSO4), and concentrated. The crude product was chromatographed (silica gel; CH2Cl2 /MeOH, 90:10) to afford the title compound as a brown oil (0.180 g, 14%): 1H NMR (CDCl3, 300 MHz) δ 1.40 (s, 9H), 1.95-2.10 (m, 4H), 3.10-3.25 (m, 2H), 4.90-5.10 (m, 1H), 6.65 (s, 1H), 7.10 (br s, 1H), 8.38 (br s, 1H); MS (DCI/NH3) m/z: 323 (M+H)+.

Workup

  1. temperaturethe mixture was heated at 60° C. for 16 hours
  2. temperatureThe reaction mixture was cooled to room temperature
  3. washwashed with Et2O (4×100 mL)
  4. washThe combined organic extracts were washed with brine/H2O (1/1 400 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customThe crude product was chromatographed (silica gel; CH2Cl2 /MeOH, 90:10)

Sources & evidence

ORD record
ord-a0618f21e0e540c8812d0b7f44ffd79c
Source dataset
uspto-grants-1999_12
Patent number
US06001849

Reaction notes

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